title: Low-mass-ion discriminant equation: a new concept for colorectal cancer screening.
abstract: Blood metabolites can be detected as low-mass ions (LMIs) by mass spectrometry (MS). These LMIs may reflect the pathological changes in metabolism that occur as part of a disease state, such as cancer. We constructed a LMI discriminant equation (LOME) to investigate whether systematic LMI profiling might be applied to cancer screening. LMI information including m/z and mass peak intensity was obtained by five independent MALDI-MS analyses, using 1,127 sera collected from healthy individuals and cancer patients with colorectal cancer (CRC), breast cancer (BRC), gastric cancer (GC) and other types of cancer. Using a two-stage principal component analysis to determine weighting factors for individual LMIs and a two-stage LMI selection procedure, we selected a total of 104 and 23 major LMIs by the LOME algorithms for separating CRC from control and rest of cancer samples, respectively. CRC LOME demonstrated excellent discriminating power in a validation set (sensitivity/specificity: 93.21%/96.47%). Furthermore, in a fecal occult blood test (FOBT) of available validation samples, the discriminating power of CRC LOME was much stronger (sensitivity/specificity: 94.79%/97.96%) than that of the FOBT (sensitivity/specificity: 50.00%/100.0%), which is the standard CRC screening tool. The robust discriminating power of the LOME scheme was reconfirmed in screens for BRC (sensitivity/specificity: 92.45%/96.57%) and GC (sensitivity/specificity: 93.18%/98.85%). Our study demonstrates that LOMEs might be powerful noninvasive diagnostic tools with high sensitivity/specificity in cancer screening. The use of LOMEs could potentially enable screening for multiple diseases (including different types of cancer) from a single sampling of LMI information.
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Jun Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Byung Chang
authors.initials: BC
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Kwang Gi
authors.initials: KG
authors.lastname: Kim
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009780:Occult Blood; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: MALDI-TOF mass spectrometry; pattern recognition; serum profiling